This application is responsive to Research Topics: 7. Sensory and Motor Processing and 13. Genetic, cellular and biochemical basis of functional senescence (including phenotypic characterization of age-related changes) The neurons of the adult brain are post-mitotic and are not replaced following injury or disease, contributing to functional decline in aging and with neurodegenerative diseases. However, the continued generation of neurons from neural stem cells in certain regions of the adult brain suggests that signals for neuronal proliferation, migration and differentiation may persist beyond development. Understanding these signals and how to regulate their expression may provide new therapeutic strategies for brain repair. Adult neurogenesis has been intensively investigated in the olfactory bulb (one of two neurogenic sites in the adult brain) of young animals. Reports investigating the dentate gyrus (the other neurogenic site) suggest that proliferation there is reduced with aging. The olfactory bulb provides a useful model for studying adult neurogenesis in that the sites of proliferation, migration, and differentiation are spatially distinct and there are three different neuronal phenotypes produced. By comparing these processes in young and aged olfactory bulb, it may be possible to detect differences that would suggest which signals are important for maintaining and regulating neurogenesis. Unfortunately, little is known about the proliferation, migration, and differentiation of neural stem cells in the aged olfactory bulb. This proposal will use multiple immunofluorescence confocal microscopy in conjunction with design-based stereology to quantify labeled progenitor cells in total and by phenotype in the aged olfactory bulb. These studies will provide a foundation for subsequent investigations into the mechanisms regulating neurogenesis in the aged olfactory bulb.